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1.  Survey Criteria for Fibromyalgia Independently Predict Increased Postoperative Opioid Consumption after Lower Extremity Joint Arthroplasty: A Prospective, Observational Cohort Study 
Anesthesiology  2013;119(6):10.1097/ALN.0b013e3182a8eb1f.
Variance in pain following total knee and hip arthroplasty may be due to a number of procedural and peripheral factors but also, in some individuals, to aberrant central pain processing as is described in conditions like fibromyalgia. To test this hypothesis, we conducted a prospective, observational cohort study of patients undergoing lower extremity joint arthroplasty.
519 patients were preoperatively phenotyped using validated self-reported pain questionnaires, psychological measures, and health information. In addition to assessing factors previously found to be associated with poor outcomes in arthroplasty, participants also completed the American College of Rheumatology survey criteria for fibromyalgia. Previous studies have suggested that rather than being “present” or “absent,” features of fibromyalgia as measured by this instrument, occur over a wide continuum. Postoperative pain control was assessed by total postoperative opioid consumption.
Preoperatively, patients with higher fibromyalgia survey scores were younger, more likely to be female, taking more opioids, reported higher pain severity, and had a more negative psychological profile. In the multivariate analysis, the fibromyalgia survey score, younger age, preoperative opioid use, knee (vs. hip), pain severity at baseline, and the anesthetic technique were all predictive of increased postoperative opioid consumption.
Using the survey criteria for fibromyalgia distinct phenotypic differences were found, and the measure was independently predictive of opioid consumption. This self-report measure may provide an additional simple means of predicting postoperative pain outcomes and analgesic requirements. Future studies are needed to determine whether tailored therapies can improve postoperative pain control in this population.
PMCID: PMC3867739  PMID: 24343289
3.  Characteristics of Chronic Pain Patients Who Take Opioids and Persistently Report High Pain Intensity 
Background and Objectives
The use of self-report questionnaires to detect characteristics of altered central pain processing, as seen in centralized pain disorders such as fibromyalgia, allow for the epidemiological studies of pain patients. Here, we assessed the relationship between reporting high levels of pain while taking opioids and the presence of characteristics associated with centralized pain.
We evaluated 582 patients taking opioid medications using validated measures of clinical pain, neuropathic pain symptoms, mood, and functioning. A multivariate linear regression model was used to assess the association between levels of pain while taking opioids and presenting with characteristics consistent with having centralized pain.
We found that 49% of patients taking opioids continued to report severe pain (≥ 7/10). In multivariate analysis, factors associated with having higher levels of pain in opioid users included higher fibromyalgia survey scores (P = 0.001), more neuropathic pain symptoms (P < 0.001), and higher levels of depression (P = 0.002). While only 3.2% were given a primary diagnosis of fibromyalgia by their physician, 40.8% met American College of Rheumatology survey criteria for fibromyalgia.
Our findings suggest that patients with persistently high pain scores despite opioid therapy are more likely than those with lower levels of pain to present with characteristics associated with having centralized pain. This study cannot determine whether these characteristics were present before (fibromyalgia-like patient) or after the initiation of opioids (opioid-induced hyperalgesia). Regardless, patients with a centralized pain phenotype are thought to be less responsive to opioids and may merit alternative approaches.
PMCID: PMC3960717  PMID: 24310048
4.  Perineural Dexmedetomidine Added to Ropivacaine for Sciatic Nerve Block in Rats Prolongs the Duration of Analgesia by Blocking the Hyperpolarization-activated Cation Current 
Anesthesiology  2011;115(4):836-843.
The present study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (Ih)current.
In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 μM or 6 μg/kg) were assessed with or without the pretreatment of α1- and α2-adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the Ih current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min post-block.
The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (Ih current) when compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90–180 min (p < 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 μM) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect.
Dexmedetomidine added to ropivacaine caused approximately a 175% increase in the duration of analgesia, which was reversed by pretreatment with an Ih current enhancer. The analgesic effect of dexmedetomidine was not reversed by an ∝2-adrenoceptor antagonist.
PMCID: PMC3179561  PMID: 21666435
5.  Fibromyalgia: A Primer for the Anesthesia Community 
Purpose of the Review
The present review is intended to give an overview of fibromyalgia for the anesthesiologist. While the basics of the treatment of fibromyalgia are included, the intent is to provide context to discuss the potential implications in perioperative management.
Recent Findings
One of the most important changes in the last year is the new criteria established by the American College of Rheumatology for the diagnosis of fibromyalgia. Instead of a combination of self-report and a tender point examination, there is a new self-report questionnaire that is now used diagnose fibromyalgia. This tool incorporates aspects of widespread body pain and some of the known comorbid symptoms. A score of 0-31 is given, which allows for the disease to be viewed as a continuum of sensitivity and symptomatology, instead of as a binary diagnosis. This continuum has been termed “fibromyalgia-ness.” This article also reviews the advances in understanding of the pathophysiology and emerging therapies. Little is known about the impact of fibromyalgia in the perioperative period.
The impact of fibromyalgia on anesthesia care is not known. Years of quality research have clearly demonstrated multiple pathophysiologic changes that could impact anesthesia care and future study is needed.
PMCID: PMC3422621  PMID: 21799404
fibromyalgia; treatment; anesthesiology; postoperative pain; chronic post-surgical pain
6.  Additives to Local Anesthetics for Peripheral Nerve Blockade 
Many additives to local anesthetics to prolong the duration of analgesia for peripheral nerve blocks have been studied. In this review, the authors focus on the more commonly described additives, including epinephrine, clonidine, dexmedetomidine, buprenorphine, dexamethasone, tramadol, sodium bicarbonate, and midazolam. While the primary focus of this review is the effect of the additive on the duration of analgesia, neurotoxicity and other safety concerns are also discussed.
PMCID: PMC3427651  PMID: 21956081
7.  Perineural Dexmedetomidine Added to Ropivacaine Causes a Dose-dependent Increase in the Duration of Thermal Antinociception in Sciatic Nerve Block in Rat 
Anesthesiology  2009;111(5):1111-1119.
The present study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would increase the duration of antinociception to a thermal stimulus in a dose-dependent fashion in a rat model of sciatic nerve blockade.
Fifty adult Sprague Dawley rats (10 rats/group) received unilateral sciatic nerve blocks with 0.2 ml of 0.5% ropivacaine or 0.2 ml of 0.5% ropivacaine plus dexmedetomidine (2.7 μM [0.5 μg/kg], 11.7 μM [2 μg/kg], 34.1 μM [6 μg/kg], or 120.6 μM [20 μg/kg]) in a randomized, blinded fashion. Time to paw withdrawal latency to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline.
Dexmedetomidine added to ropivacaine increased the duration of dense sensory blockade and time for return to normal sensory function in a dose-dependent fashion (p < 0.005). There was a significant time (p < 0.005), dose (p < 0.005), and time by dose effect (p < 0.005) on paw withdrawal latencies of the operative paws. There were no significant differences in paw withdrawal latencies of the control paws, indicating little systemic effect of the dexmedetomidine. The duration of motor blockade was also increased with dexmedetomidine. High-dose dexmedetomidine (120.6 μM) was not neurotoxic.
This is the first study showing that dexmedetomidine added to ropivacaine increases the duration of sensory blockade in a dose-dependent fashion in rat. The findings are an essential first step encouraging future efficacy studies in humans.
PMCID: PMC2770892  PMID: 19858875
8.  A Prospective, Observational Study of the Relationship Between Body Mass Index and Depth of the Epidural Space During Lumbar Transforaminal Epidural Steroid Injection 
Background and Objectives
Previous studies have concluded that transforaminal epidural steroid injections (ESIs) are more effective than interlaminar injections in the treatment of radiculopathies due to lumbar intervertebral disk herniation. There are no published studies examining the depth of epidural space using a transforaminal approach. We investigated the relationship between body mass index (BMI) and the depth of the epidural space during lumbar transforaminal ESIs.
Eighty-six consecutive patients undergoing lumbar transforaminal ESI at the L3-L4, L4-L5, and L5-S1 levels were studied. Using standard protocol, the foraminal epidural space was attained using fluoroscopic guidance. The measured distance from needle tip to skin was recorded (depth to foraminal epidural space). The differences in the needle depth and BMI were analyzed using regression analysis.
Needle depth was positively associated with BMI (regression coefficient [RC], 1.13; P < 0.001). The median depths (in centimeters) to the epidural space were 6.3, 7.5, 8.4, 10.0, 10.4, and 12.2 for underweight, normal, preobese, obese I, obese II, and obese III classifications, respectively. Sex (RC, 1.3; P = 0.02) and race (RC, 0.8; P = 0.04) were also significantly associated with needle depth; however, neither factor remained significant when BMI was accounted as a covariate in the regression model. Age, intervertebral level treated, and oblique angle had no predictive value on foraminal depth (P > 0.2).
There is a positive association between BMI and transforaminal epidural depth, but not with age, sex, race, oblique angle, or intervertebral level.
PMCID: PMC2715548  PMID: 19282707
9.  Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in the Rat 
Anesthesiology  2008;109(3):502-511.
The present study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.
Thirty-one adult Sprague Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml of 0.5% bupivacaine and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral leg, or 0.2 ml of 0.005% dexmedetomidine and normal saline in the contralateral leg. Sensory and motor function were assessed by a blinded investigator every 30 minutes until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 hours or 14 days after injection and analyzed for perineural inflammation and nerve damage.
High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 hours and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 hours than the bupivacaine group when compared with the saline control.
The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception following sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade, therefore future work with clinically relevant doses is necessary.
PMCID: PMC2709835  PMID: 18719449
10.  Buprenorphine Disrupts Sleep and Decreases Adenosine Levels in Sleep-Regulating Brain Regions of Sprague Dawley Rat 
Anesthesiology  2011;115(4):743-753.
Buprenorphine, a partial μ opioid receptor agonist and κ opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine levels in regions of the basal forebrain and pontine brain stem that regulate sleep.
Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep/wake states were recorded for 24 h. In additional rats buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while simultaneously measuring adenosine.
An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in both nonrapid eye movement sleep (−22.1%) and rapid eye movement sleep (−3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative/hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine levels in the pontine reticular formation (−14.6%) and substantia innominata (−36.7%). Intravenous administration of buprenorphine significantly decreased (−20%) adenosine in the substantia innominata.
Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative/hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine levels in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.
PMCID: PMC3197808  PMID: 21857500

Results 1-10 (10)